{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:59:05Z","timestamp":1791831545239,"version":"4.3.4"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T00:00:00Z","timestamp":1601424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100008253","name":"Shaoxing University","doi-asserted-by":"publisher","award":["20185009"],"award-info":[{"award-number":["20185009"]}],"id":[{"id":"10.13039\/501100008253","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>) exposure can induce hepatic ductular reactions. To date, however, the related mechanism remains largely unknown. Sonic hedgehog (Shh) and Yes\u2010associated protein (Yap) signaling are correlated with liver injury and regeneration. Herein, we investigated the role of Shh and Yap signaling in the fate of ductular reaction cells in CCl<jats:sub>4<\/jats:sub>\u2010treated livers and the possible mechanisms. Wild\u2010type and Shh\u2010EGFP\u2010Cre male mice were exposed to CCl<jats:sub>4<\/jats:sub> (2\u2009mL\/kg), and then treated with or without the Shh signaling inhibitor Gant61. The level of liver injury, proliferation of ductular reaction cells, and expression levels of mRNA and protein related to the Shh and Yap signaling components were assessed. Results showed that CCl<jats:sub>4<\/jats:sub> treatment induced liver injury and promoted activation and proliferation of ductular reaction cells. In addition, CCl<jats:sub>4<\/jats:sub> induced the expression of Shh ligands in hepatocytes, accompanied by activation of Shh and Yap1 signaling in the liver. Furthermore, administration of Gant61 ameliorated liver regeneration, inhibited hepatic ductular reactions, and decreased Shh and Yap1 signaling activity. Thus, Shh\u2010Yap1 signaling appears to play an integral role in the proliferation of ductular reaction cells in CCl<jats:sub>4<\/jats:sub>\u2010induced liver injury. This study should improve our understanding of the mechanism of CCl<jats:sub>4<\/jats:sub>\u2010induced liver injury and ductular reactions and provide support for future investigations on liver disease therapy.<\/jats:p>","DOI":"10.1002\/tox.23025","type":"journal-article","created":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T13:02:54Z","timestamp":1601470974000},"page":"194-203","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["<scp>Shh\u2010Yap<\/scp> signaling controls hepatic ductular reactions in <scp>CCl<sub>4<\/sub><\/scp>\u2010induced liver injury"],"prefix":"10.1002","volume":"36","author":[{"given":"Lifang","family":"Jin","sequence":"first","affiliation":[{"name":"School of Life Science Shaoxing University  Shaoxing Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huarong","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Life and 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